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Human leucocyte antigen class I in hormone receptor-positive, HER2-negative breast cancer: association with response and survival after neoadjuvant chemotherapy.
Breast Cancer Research ( IF 7.4 ) Pub Date : 2019-12-11 , DOI: 10.1186/s13058-019-1231-z
Bruno Valentin Sinn 1, 2 , Karsten E Weber 3 , Wolfgang Daniel Schmitt 1 , Peter A Fasching 4 , William Fraser Symmans 5 , Jens-Uwe Blohmer 6 , Thomas Karn 7 , Eliane Tabea Taube 1 , Frederick Klauschen 1, 8 , Frederik Marmé 9 , Christian Schem 10, 11 , Elmar Stickeler 12 , Beyhan Ataseven 13, 14 , Jens Huober 15 , Gunter von Minckwitz 3 , Barbara Seliger 16 , Carsten Denkert 1, 8, 17 , Sibylle Loibl 3
Affiliation  

BACKGROUND Clinical application of cancer immunotherapy requires a better understanding of tumor immunogenicity and the tumor microenvironment. HLA class I molecules present antigens to CD8+ cytotoxic cells. Their loss or downregulation is frequently found in tumors resulting in reduced T cell responses and worse prognosis. METHODS We evaluated HLA class I heavy chain expression by immunohistochemistry in 863 biopsies (GeparTrio trial). Patients received neoadjuvant chemotherapy and adjuvant endocrine treatment if tumors were hormone receptor-positive (HR+). In parallel, the expression of HLA-A was analyzed using a microarray cohort of 320 breast cancer patients from the MD Anderson Cancer Center. We evaluated its association with clinical outcome, tumor-infiltrating lymphocytes (TILs), and immune cell metagenes. RESULTS In HR+/HER2- breast cancer, HLA class I heavy chain expression was associated with increased TILs and better response to chemotherapy (7% vs. 14% pCR rate, P = 0.029), but worse disease-free survival (hazard ratio (HR) 1.6 (1.1-2.4); P = 0.024). The effect was significant in a multivariate model adjusted for clinical and pathological variables (HR 1.7 (1.1-2.6); P = 0.016) and was confirmed by analysis of HLA-A in a microarray cohort. HLA-A was correlated to most immune cell metagenes. There was no association with response or survival in triple-negative or HER2+ disease. CONCLUSIONS The study confirms the negative prognostic role of lymphocytes in HR+ breast cancer and points at a complex interaction between chemotherapy, endocrine treatment, and tumor immunogenicity. The results point at a subtype-specific and potentially treatment-specific role of tumor-immunological processes in breast cancer with different implications in triple-negative and hormone receptor-positive disease.

中文翻译:

激素受体阳性,HER2阴性乳腺癌中的人类白细胞抗原I类:与新辅助化疗后的反应和生存相关。

背景技术癌症免疫疗法的临床应用需要对肿瘤免疫原性和肿瘤微环境有更好的了解。HLA I类分子将抗原呈递给CD8 +细胞毒性细胞。在肿瘤中经常发现它们的丢失或下调,从而导致T细胞反应降低和预后不良。方法我们通过免疫组织化学在863活检中评估了HLA I类重链表达(GeparTrio试验)。如果肿瘤是激素受体阳性(HR +),则患者接受新辅助化疗和辅助内分泌治疗。平行地,使用来自MD安德森癌症中心的320名乳腺癌患者的微阵列队列分析了HLA-A的表达。我们评估了其与临床结局,肿瘤浸润淋巴细胞(TIL)和免疫细胞亚基因的关系。结果在HR + / HER2-乳腺癌中,HLA I类重链表达与TIL增加和对化疗的反应更好有关(7%vs.14%pCR率,P = 0.029),但无病生存期较差(危险比( HR)1.6(1.1-2.4); P = 0.024)。在针对临床和病理变量进行调整的多变量模型中(HR 1.7(1.1-2.6); P = 0.016),该效果显着,并且通过在微阵列队列中对HLA-A的分析得到了证实。HLA-A与大多数免疫细胞的基因有关。三阴性或HER2 +疾病与反应或生存无关。结论该研究证实了淋巴细胞在HR +乳腺癌中的负预后作用,并指出了化学疗法,内分泌治疗和肿瘤免疫原性之间的复杂相互作用。
更新日期:2020-04-22
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